Anti-hypertensives: Landmark study data to drive sales

Heart failure as an indication has attracted considerable investment from companies seeking to expand the patient potential of their anti-hypertensives, with diuretics, ACE inhibitors and beta blockers all being approved and widely recommended for heart failure. Despite the number of agents already approved for this indication, the increasing prevalence of the disease has ensured that it remains an attractive target for drug makers.

In an extremely competitive market, pharmaceutical companies have been forced to develop their anti-hypertensive drugs for additional indications in order to expand their potential patient population. Several recent landmark trials have focused on the benefits of anti-hypertensives beyond blood pressure control but it is unlikely that all of these treatments will be successful.

In the Market Brief 'Anti-hypertensives: Landmark trials update', Datamonitor provides a critical analysis of these landmark trials, along with updated sales forecasts to 2011 for the drugs concerned. The brief examines the potential for angiotensin receptor blockers (ARBs) in heart failure and looks at Pfizer's Inspra following its recent expanded approval.

Three of these trials, CHARM, COMET and EPHESUS, have focused on heart failure, where unmet needs remain high in terms of improving symptoms and quality of life, reducing costly hospitalizations and decreasing mortality. The fourth trial, EUROPA, looked at the coronary artery disease (CAD) population to assess whether the benefits of ACE inhibitors in high-risk patients, demonstrated in the HOPE trial, also apply to lower-risk populations.  

Market battle

The CHARM and EPHESUS trial results showed significant benefits for, AstraZeneca's ARB, Atacand (candesartan), and Pfizer's selective aldosterone receptor antagonist (SARA), Inspra (eplerenone), when added to standard therapy for heart failure. Resolving the debate about whether ‘excessive’ blockade of the renin angiotensin aldosterone system is detrimental, these trial results have the potential to drive use of these agents substantially.

However, physicians fail to optimally prescribe current therapies and will be concerned about the effects on patient compliance of further increasing the pill burden. Although Atacand will benefit from its side effect profile, it faces the barrier that many physicians will assume class effects and prescribe other ARBs.

Meanwhile, Inspra's superior tolerability compared to spironolactone should enable use of the drug to exceed that of its predecessor, although Pfizer will have to effectively differentiate eplerenone and address concerns about hyperkalemia with physician education on patient monitoring and dose titration.

The market success of Atacand is expected to continue, but whilst AstraZeneca's drug is already approved for the treatment of hypertension it is not currently indicated for heart failure. Approved for both heart failure and hypertension and supported by Pfizer’s marketing capabilities, Datamonitor forecasts that Inspra will achieve blockbuster status in 2008, just four years after launch.

Beta blockers and ACE inhibitors

ARBs are however, not the only class of drugs to be supported by landmark data for the treatment of heart failure. The COMET trial demonstrated the potential of carvedilol and beta blockers in general.

Carvedilol benefits from being supported by the greatest amount of clinical trial data in heart failure, having gained indications in the whole spectrum of the disease ranging from post-myocardial infarction patients with left ventricular dysfunction to severe cases of heart failure. The COMET results provide GlaxoSmithKline and Roche with an effective marketing tool and are likely to mean that carvedilol becomes the therapy of choice for new patients.

The EUROPA trial meanwhile, which demonstrated a 20% reduction in the primary endpoint of cardiovascular death, MI and cardiac arrest, should dramatically expand the use of ACE inhibitors. The trial was believed to answer many of the questions that remained following the HOPE trial.

Trials to continue

Growth of both older and newer anti-hypertensives classes alike continues to be driven by the fact that the vast majority of patients require combination therapy to control blood pressure, or for co-morbid conditions where anti-hypertensives are also indicated.

Demonstrating benefits beyond blood pressure lowering has been crucial in determining the success of ACE inhibitors and beta blockers and the lack of additional cardio and reno protective benefits largely explains the relegation of calcium channel blockers to later lines of therapy.

As drugs in older classes continue to lose patent protection, with the leading anti- hypertensive Norvasc set to be genericized from 2007, ARBs and new drugs, such as

Inspra, will be the sole drivers of growth in the anti-hypertensives market. The benefits that these drugs have already demonstrated beyond blood pressure lowering will serve to substantially increase their patient population and market uptake.

This is particularly the case for trials such as CHARM and EPHESUS, which have demonstrated additional benefits for newer drugs when added to established therapies, including ACE inhibitors. However, as the focus for investment, these drugs are also involved in numerous other trials further investigating benefits beyond blood pressure control throughout the cardiovascular continuum. The results of these trials will also be highly influential and are eagerly awaited.

If you found this week's Expert View useful, you may be interested in Datamonitor's reports:

• Anti-hypertensives: Landmark clinical trial update - priced $1,600
• 2003 Cardiovascular Market Update: Part 1 - Anti-hypertensives, Anti-dyslipidemics and Cardiac Therapy priced $1,600
• Market Dynamics: Anti-hypertensives - ALLHAT 'Landmark' Trial Old Hat?priced $12,800

To order these reports contact peter.barfoot@bioportfolio.com or telephone +44 1300 321501 or +1 415 680 2472 and a representative will get back to you.